chr11-17593282-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001292063.2(OTOG):c.3096C>T(p.Asn1032Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,550,482 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 7 hom., cov: 33)

Exomes 𝑓: 0.013 ( 135 hom. )

Consequence

OTOG
NM_001292063.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.85

Variant links:

Genes affected

OTOG (HGNC:8516): (otogelin) The protein encoded by this gene is a component of the acellular membranes of the inner ear. Disruption of the orthologous mouse gene shows that it plays a role in auditory and vestibular functions. It is involved in fibrillar network organization, the anchoring of otoconial membranes and cupulae to the neuroepithelia, and likely in sound stimulation resistance. Mutations in this gene cause autosomal recessive nonsyndromic deafness, type 18B. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

OTOG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 11-17593282-C-T is Benign according to our data. Variant chr11-17593282-C-T is described in ClinVar as [Benign]. Clinvar id is 226878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.85 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00927 (1412/152308) while in subpopulation NFE AF= 0.0153 (1043/68026). AF 95% confidence interval is 0.0146. There are 7 homozygotes in gnomad4. There are 662 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOG	NM_001292063.2 link	c.3096C>T	p.Asn1032Asn	synonymous_variant	Exon 26 of 56	ENST00000399397.6	NP_001278992.1	H9KVB3
OTOG	NM_001277269.2 link	c.3132C>T	p.Asn1044Asn	synonymous_variant	Exon 25 of 55		NP_001264198.1	Q6ZRI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTOG	ENST00000399397.6 link	c.3096C>T	p.Asn1032Asn	synonymous_variant	Exon 26 of 56	5	NM_001292063.2	ENSP00000382329.2	H9KVB3
OTOG	ENST00000399391.7 link	c.3132C>T	p.Asn1044Asn	synonymous_variant	Exon 25 of 55	5		ENSP00000382323.2	Q6ZRI0-1
OTOG	ENST00000342528.2 link	n.461C>T		non_coding_transcript_exon_variant	Exon 3 of 22	2

Frequencies

GnomAD3 genomes

AF:

0.00928

AC:

1412

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00844

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0153

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00978

AC:

1459

AN:

149248

Hom.:

AF XY:

0.0102

AC XY:

823

AN XY:

80384

show subpopulations

Gnomad AFR exome

AF:

0.00133

Gnomad AMR exome

AF:

0.00635

Gnomad ASJ exome

AF:

0.0201

Gnomad EAS exome

AF:

0.0000927

Gnomad SAS exome

AF:

0.00657

Gnomad FIN exome

AF:

0.00291

Gnomad NFE exome

AF:

0.0159

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.0127

AC:

17807

AN:

1398174

Hom.:

135

Cov.:

AF XY:

0.0127

AC XY:

8728

AN XY:

689618

show subpopulations

Gnomad4 AFR exome

AF:

0.00215

Gnomad4 AMR exome

AF:

0.00770

Gnomad4 ASJ exome

AF:

0.0197

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.00641

Gnomad4 FIN exome

AF:

0.00309

Gnomad4 NFE exome

AF:

0.0143

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.00927

AC:

1412

AN:

152308

Hom.:

Cov.:

AF XY:

0.00889

AC XY:

662

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00272

Gnomad4 AMR

AF:

0.00837

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00622

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.0153

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.0135

Hom.:

Bravo

AF:

0.0100

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 16, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

OTOG: BP4, BP7, BS1, BS2 -

not specified

Benign:1

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Asn1044Asn in exon 25 of OTOG: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 4.5% (5/110) of Pue rto Rican chromosomes from a broad population by the 1000 Genomes Project (http: //www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs75133799). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

0.45

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over